De Groot Anne S, Moise Lenny, Liu Rui, Gutierrez Andres H, Terry Frances, Koita Ousmane A, Ross Ted M, Martin William
Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA; EpiVax, Inc.; Providence, RI USA.
Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA.
Hum Vaccin Immunother. 2014;10(2):256-62. doi: 10.4161/hv.28135. Epub 2014 Feb 13.
A novel avian-origin H7N9 influenza strain emerged in China in April 2013. Since its re-emergence in October-November 2013, the number of reported cases has accelerated; more than 220 laboratory-confirmed cases and 112 deaths (case fatality rate of 20-30%) have been reported. The resurgence of H7N9 has re-emphasized the importance of making faster and more effective influenza vaccines than those that are currently available. Recombinant H7 hemagglutinin (H7-HA) vaccines have been produced, addressing the first problem. Unfortunately, these recombinant subunit vaccine products appear to have failed to address the second problem, influenza vaccine efficacy. Reported unadjuvanted H7N9 vaccine seroconversion rates were between 6% and 16%, nearly 10-fold lower than rates for unadjuvanted vaccine seroconversion to standard H1N1 monovalent (recombinant) vaccine (89% to pandemic H1N1). Could this state of affairs have been predicted? As it turns out, yes, and it was. In that previous analysis of available H7-HA sequences, we found fewer T-cell epitopes per protein than expected, and predicted that H7-HA-based vaccines would be much less antigenic than recent seasonal vaccines. Novel approaches to developing a more immunogenic HA were offered for consideration at the time, and now, as the low immunogenicity of H7N9 vaccines appears to indicate, they appear to be even more relevant. More effective H7N9 influenza vaccines can be produced, provided that the role of T-cell epitopes is carefully considered, and accumulated knowledge about the importance of cross-conserved epitopes between viral subtypes is applied to the design of those vaccines.
2013年4月，一种新型禽源H7N9流感毒株在中国出现。自2013年10月至11月再次出现以来，报告病例数加速上升；已报告超过220例实验室确诊病例和112例死亡（病死率为20%-30%）。H7N9的卷土重来再次凸显了研发比现有疫苗更快、更有效的流感疫苗的重要性。重组H7血凝素（H7-HA）疫苗已经生产出来，解决了第一个问题。不幸的是，这些重组亚单位疫苗产品似乎未能解决第二个问题，即流感疫苗的效力。报告的未添加佐剂的H7N9疫苗血清转化率在6%至16%之间，比未添加佐剂的疫苗针对标准H1N1单价（重组）疫苗（89%至大流行性H1N1）的血清转化率低近10倍。这种情况能够被预测到吗？事实证明，是可以的，而且也的确被预测到了。在之前对可用H7-HA序列的分析中，我们发现每个蛋白质的T细胞表位比预期的少，并预测基于H7-HA的疫苗的抗原性将远低于近期的季节性疫苗。当时就提出了开发更具免疫原性的HA的新方法以供考虑，而现在，由于H7N9疫苗的低免疫原性似乎表明了这一点，这些方法似乎更加重要。只要仔细考虑T细胞表位的作用，并将积累的关于病毒亚型之间交叉保守表位重要性的知识应用于这些疫苗的设计，就能够生产出更有效的H7N9流感疫苗。
